A broadly neutralizing human monoclonal antibody against the hemagglutinin of avian influenza virus H7N9 / 中华医学杂志(英文版)

BACKGROUND@#The new emerging avian influenza A H7N9 virus, causing severe human infection with a mortality rate of around 41%. This study aims to provide a novel treatment option for the prevention and control of H7N9.@*METHODS@#H7 hemagglutinin (HA)-specific B cells were isolated from peripheral blood plasma cells of the patients previously infected by H7N9 in Jiangsu Province, China. The human monoclonal antibodies (mAbs) were generated by amplification and cloning of these HA-specific B cells. First, all human mAbs were screened for binding activity by enzyme-linked immunosorbent assay. Then, those mAbs, exhibiting potent affinity to recognize H7 HAs were further evaluated by hemagglutination-inhibiting (HAI) and microneutralization in vitro assays. Finally, the lead mAb candidate was selected and tested against the lethal challenge of the H7N9 virus using murine models.@*RESULTS@#The mAb 6-137 was able to recognize a panel of H7 HAs with high affinity but not HA of other subtypes, including H1N1 and H3N2. The mAb 6-137 can efficiently inhibit the HA activity in the inactivated H7N9 virus and neutralize 100 tissue culture infectious dose 50 (TCID50) of H7N9 virus (influenza A/Nanjing/1/2013) in vitro, with neutralizing activity as low as 78 ng/mL. In addition, the mAb 6-137 protected the mice against the lethal challenge of H7N9 prophylactically and therapeutically.@*CONCLUSION@#The mAb 6-137 could be an effective antibody as a prophylactic or therapeutic biological treatment for the H7N9 exposure or infection.

Meta-analysis on effectiveness of live attenuated influenza vaccine against seasonal influenza in children / 中华流行病学杂志

Objective@#To evaluate the effectiveness of live attenuated influenza vaccine (LAIV) in the prevention of seasonal influenza in children aged 2-17 years.@*Methods@#Literature retrieval of case-control studies on the effectiveness of LAIV against seasonal influenza in children published from January 2003 to November 2018 was conducted through Web of Science, PubMed, and ScienceDirect databases. The Stata 13.1 software was used for Meta-analysis.@*Results@#A total of 14 studies were included in this study, and all were test-negative design (TND) studies. Our Meta-analysis showed that the effectiveness of LAIV in children was 49% (95%CI: 40%-57%). Subgroup analysis found that the protection rate of LAIV was 35% against influenza A (H1N1) pdm09 (95%CI: 5%-56%), 35% against influenza A (H3N2) (95%CI: 21%-46%), and 71% against influenza B (95%CI: 55%-82%). The protection rates of trivalent LAIV and quadrivalent LAIV in children were 56% (95%CI: 48%-63%) and 44% (95%CI: 27%-57%), respectively. The protection rates of LAIV in Europe and North America were 65% (95%CI: 47%-77%) and 46% (95%CI: 36%-55%), respectively.@*Conclusion@#LAIV has a certain preventive effect on seasonal influenza in children aged 2-17 years.

Construction and application of EV71 ScFv high-throughput cassette expression system / 中华实验和临床病毒学杂志

Objective@#To construct a method to express ScFv antibody from PCR products, and use it in phage display for high-throughput ScFv expression.@*Methods@#Cytomegalovirus (CMV) promotor, ScFv and BGH-Poly A gene fragments were amplified by PCR. Overlapping PCR was used to form a tandemly linear cassette gene. By transiently transfected into 293T cells, ScFv antibodies expression of cassette gene were tested by Western blot, enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescent antibody (IFA). Ninety-six clones of antibody genes in phage library were selected and expressed by cassette expression system. The expression level was evaluated and analyzed.@*Results@#Three fragments were obtained and a cassette expression system formed. Cassette expression system worked successfully in 293T cells, as a Mr.38×103 brand could observed in Western blot assay. The expressed antibody could specifically bind to its antigen by result of ELISA and IFA. This cassette expression system could also be used in phage display for high-throughput panning.@*Conclusions@#The cassette expression system was constructed successfully and high-throughput antibody expression has been achieved.

Research progress of maternal immunization / 中华预防医学杂志

Maternal immunization is an immune strategy that protects both mothers and early-life infants from disease by the vaccination of pregnant women. The effect of maternal immunization is influenced by the types of vaccines, the timing of vaccination, the subtypes of antibodies induced by vaccines, and the health status of mothers themselves. Inactivated influenza vaccination during pregnancy and DPT vaccination during the third trimester of pregnancy have been widely used in the world, while Hepatitis B vaccine, pneumococcal and meningococcal vaccines also show good efficacy and safety in pregnant women. This article reviews the research progress of Maternal Immunization in order to provide a reference for Maternal Immunization planning and policymaking in China.

Original antigenic sin in the influenza vaccination and its influence / 中华预防医学杂志

Original antigenic sin may exist in the influenza virus infection or vaccination, which possibly reduces the protective efficacy in repeated influenza vaccination. This paper reviews the literature on the original antigenic sin and its influence in influenza vaccination, and interprets the possible mechanism of this phenomenon from the three aspects of influenza virus structure, humoral immunity and cellular immunity. A large number of studies have shown that original antigen sin has a negative impact on influenza vaccination, but the evidence disproveing this phenomenon also exist, so multi-center large-scale clinical trials should be conducted to provide evidence-based basis for reaearching whether original antigen sin exists and its effects. in order to provide reference for the development and update of noval influenza vaccines and its formulation of immunization strategies.

Research progress of the surrogate of protection of pneumococcal conjugate vaccine / 中华预防医学杂志

There are many limitations in evaluating vaccine efficacy by comparing the incidence of clinical endpoint events (such as morbidity, bacterial colonization) between the vaccine group and the control group. Therefore, the researchers put forward the concept of Surrogate of protection to predict vaccine protection with immunological indicators. In 2012, WHO put forward the immunological substitution endpoint of pneumococcal vaccine, using 0. 35 μg/ml as the protective antibody level of pneumococcal vaccine. But subsequent studies have found that using this threshold to assess all vaccine serotypes may not be accurate.

Interpretation for diagnosis of Yersiniosis / 中华流行病学杂志

Yersiniosis is one of the "other infectious diarrhea" of the notifiable infectious diseases and also an important food-borne disease. However, it lacked the basis or standard for diagnosis. The Chinese Preventive Medicine Association coordinated experienced researchers from National Institute for Communicable Disease Control and Prevention, China CDC and other institutes to produce the group standard entitled "Diagnosis of Yersiniosis" (T/CPMA 005-2019). Based on the principle of "legality, scientificity, advancement, and feasibility" , the standard gives a clear definition for Yerisiniosis, stipulates diagnosis basis, principles and main differential diagnosis and provides two informative appendixes for epidemiological and clinical characteristics and a normative appendix for laboratory detection. The standard provides accurate basis and methods of Yersiniosis diagnosis for hospitals and CDCs at all levels in China. It will solve the problems that Yersiniosis cannot be clearly diagnosed for clinical cases and in the outbreaks.

Progress in research of influence of gene polymorphisms on immune response / 中华流行病学杂志

Genes play an important role in the immune system response,and different gene loci may result in different vaccine immune response rates.This review focuses on the correlation between gene polymorphisms and vaccine immune response in order to investigate the influence of gene polymorphisms on the immune response to vaccines.It discusses the effect of an individual's immune response after vaccination at genetic level and provides a scientific basis for individualized immune development strategies.It reveals that human leukocyte antigen genes,various cytokines and their receptor genes,and Toll-like receptor genes all affect the vaccine immune response.

Progress in assessment of vaccine on herd protection / 中华流行病学杂志

The importance of vaccine on public health is related to the herd protection related to the levels of vaccine coverage,which directly influences the vaccinated individuals as well as the unvaccinated community.Reaching the level of herd protection by increasing vaccine coverage is the basic strategy to eradicate related infectious diseases.Again,herd protection has played an important role in public health practices.With the increasing interests in estimating the vaccine herd protection,we however,have seen only few relevant papers including observational population-based and cluster-randomized clinical trials reported in China.We hope to discuss the study designs for evaluating the vaccine herd protection in order to generate evidence-based related research in this field.

Progress in research of vaccination for patients with cancer / 中华流行病学杂志

Due to the tumor malignancy or immunosuppressive treatment,patients with cancer in general are more susceptible to vaccine-preventable infections.The types,timing,dose of vaccination or even the immunization program for them may differ from those for the normal persons.At present,it is recommended to use inactivated vaccines for patients with cancer rather than attenuated live vaccines,Vaccinations should be avoided during immunosuppressive therapy;patients with cancer should receive double dosage of hepatitis B vaccines and two doses of inactivated influenza vaccines yearly.This paper summarizes the progress in clinical trials of vaccination for cancer patients in foreign countries,and provide reference for the development and implementation of vaccination strategy for cancer patients in China.

Research progress in immunization status and immunization effect of preterm infants / 中华预防医学杂志

Due to immature development of the immune system, preterm infants are at increased risk of infections from vaccine-preventable diseases. But at the same time, premature vaccination may not induce a good immune response because of the incomplete development of the neonatal immune system, and may cause serious adverse reactions risk due to the poor immune tolerance, thus vaccination of preterm infants at the appropriate time is the key to reducing the risk of infectious disease and obtaining vaccine protection. At present, it is generally recommended that the gestational age and birth weight should be considered in the vaccination of preterm infants. The timing, type and even the immunization schedule of the vaccine should be differ from that of the full term infants. However, there is a lack of research results and data on immunization program in preterm infants in China, and there is still no provided universal guidelines for their vaccine immunization. This article aims to summarize the guidelines and clinical trials of vaccination of preterm infants in foreign countries, and to provide reference for the formulation and implementation of immunization strategies for preterm infants in China.

Investigation on the effects of booster immunization of human diploid cell rabies vaccine after eight years of primary vaccination / 中华实验和临床病毒学杂志

Objective@#To disclose the effects of booster immunization of human diploid cell rabies vaccine (HDCV) after eight years of primary vaccination.@*Methods@#Sixty subjects who had participated the phase Ⅲ clinical trial of freeze-dried HDCV were selected and gaven booster immunization after eight years of primary vaccination. The side effects of booster immunization were observed. The serum before and after 14 days of booster immunization were collected and detected the rabies virus neutralizing antibody (RVNA) by rapid fluorescent focus inhibition test (RFFIT). The positive rate and geometric mean titer (GMT) of RVNA before and after booster immunization were made statistical analysis.@*Results@#Total 54 subjects finished the follow-up and RVNA detection. No sever side-effects were observed in 30 min or 15 days of follow-up after booster immunization. The positive rate of RVNA before and after booster immunization were 51.85% (28/54) and 96.30% (52/54). The GMT of RVNA before and after booster immunization were 1.42 IU/ml and 30.61 IU/ml.@*Conclusions@#The freeze-dried HDCV has good immune effects with one-dose of booster immunization after eight years of primary vaccination.

Progress in research of influence of gene polymorphisms on immune response / 中华流行病学杂志

Genes play an important role in the immune system response,and different gene loci may result in different vaccine immune response rates.This review focuses on the correlation between gene polymorphisms and vaccine immune response in order to investigate the influence of gene polymorphisms on the immune response to vaccines.It discusses the effect of an individual's immune response after vaccination at genetic level and provides a scientific basis for individualized immune development strategies.It reveals that human leukocyte antigen genes,various cytokines and their receptor genes,and Toll-like receptor genes all affect the vaccine immune response.

Progress in assessment of vaccine on herd protection / 中华流行病学杂志

The importance of vaccine on public health is related to the herd protection related to the levels of vaccine coverage,which directly influences the vaccinated individuals as well as the unvaccinated community.Reaching the level of herd protection by increasing vaccine coverage is the basic strategy to eradicate related infectious diseases.Again,herd protection has played an important role in public health practices.With the increasing interests in estimating the vaccine herd protection,we however,have seen only few relevant papers including observational population-based and cluster-randomized clinical trials reported in China.We hope to discuss the study designs for evaluating the vaccine herd protection in order to generate evidence-based related research in this field.

Progress in research of vaccination for patients with cancer / 中华流行病学杂志

Due to the tumor malignancy or immunosuppressive treatment,patients with cancer in general are more susceptible to vaccine-preventable infections.The types,timing,dose of vaccination or even the immunization program for them may differ from those for the normal persons.At present,it is recommended to use inactivated vaccines for patients with cancer rather than attenuated live vaccines,Vaccinations should be avoided during immunosuppressive therapy;patients with cancer should receive double dosage of hepatitis B vaccines and two doses of inactivated influenza vaccines yearly.This paper summarizes the progress in clinical trials of vaccination for cancer patients in foreign countries,and provide reference for the development and implementation of vaccination strategy for cancer patients in China.

Analysis of virulence genes and the chromosomal 16S rRNA gene polymorphism of Yersinia enterocolitic in Jiangsu Province,2015 / 中华传染病杂志

Objective To reveal the virulence genes and the polymorphisms of chromosomal 16S rRNA gene of Yersinia enterocolitic strains isolated from different districts in Jiangsu Province,2015. Methods Five virulence genes(ail,virF,yadA,ystA and ystB)of Yersinia enterocolitic strains isolated from different districts in Jiangsu Province were detected by using polymerase chain reaction(PCR),and phylogenetic analysis of chromosomal 16S rRNA gene was performed by amplification and sequencing. Results In this study,73 Yersinia enterocolitic strains were collected in Jiangsu Province in 2015.Among them,56(76.7%)strains carried virulence genes,and ail-virF-yadA -ystA -ystB+were the dominate types in diarrhea patients and other hosts.All strains can be clustering into 4 groups according to the phylogenetic analysis of chromosomal 16S rRNA gene.Conclusions The non-pathogenic Yersinia enterocolitic(ystB+)is the dominant strain in Jiangsu province,and the pathogenic strains are also found in this region.The result of phylogenetic analysis of chromosomal 16S rRNA gene and the profiles of virulence genes are highly consistent.

Correlation between intestinal microbiota and immune response to vaccination / 中华微生物学和免疫学杂志

Intestinal microbiota plays an important role in the development of immune system,es-pecially in the formation of immune response. Immune response to vaccination varies with region and popula-tion,which may be related to the differences in intestinal microbiota. This review focused on the correlation between intestinal microbiota and immune response to vaccination in order to find a new way to enhance vac-cine-induced immune response. It was revealed that intestinal microbiota might be involved in the immune responses to vaccines against rotavirus, typhoid and polio. Although probiotics, prebiotics and synbiotics could not significantly enhance vaccine-induced immune response,they might have a beneficial effect on vac-cine by regulating intestinal microbiota.

Rapid detection of human adenovirus by recombinase polymerase amplification assay and lateral flow dipstick / 中华实验和临床病毒学杂志

Objective@#To establish a rapid and sensitive isothermal amplification assay for the detection of human Adenovirus.@*Methods@#Primers and probe used for recombinase polymerase amplification(RPA)were designed based on the conserved region of the adenoviruses hexon gene. After optimizing the reaction temperature and times, the products of RPA were detected by capillary electrophoresis and lateral flow dipstick(LFD). Sensitivity and specicity of the assay were evaluated. The diagnostic value of the RPA-LFD assay was verified using clinical samples which were simultaneously tested by real time PCR assay.@*Results@#The analytical sensitivity of RPA-LFD assay was 2 copies DNA molecules per reaction and no cross reaction with other pathogens was observed. Compared with real-time PCR assay, the sensitivity, and specificity of the present assay were all 100%.@*Conclusions@#The RPA-LFD assay developed in this study has the characteristics of high specificity, sensitivity, rapid and no requirement of expensive equipment which provided a new tool for rapid detection of human adenovirus.

Detection of neutralizing antibodies and DNA of human papillomavirus 16, 18 in women aged 18-45 years in Funing, Jiangsu province / 中华流行病学杂志

<p><b>OBJECTIVE</b>To understand the distributions of DNA and neutralizing antibodies of human papillomavirus (HPV)16, 18 in 18-45 year-old women.</p><p><b>METHODS</b>Totally, 1494 women were enrolled through multistage random sampling in Funing, Jiangsu province. Cervical exfoliated cells were collected from them for HPV DNA testing, and serum samples were taken from them for the detection of HPV16, 18 neutralizing antibodies by using pseudovirion-based neutralization assay(PBNA).</p><p><b>RESULTS</b>Among the 1494 women, 28(1.9%) and 188(12.6%) were positive for DNA and neutralizing antibody of HPV16 respectively, and 15(1.0%) and 60(4.0%) were positive for DNA and neutralizing antibody of HPV18, respectively. There were no significant differences in the detection rates of DNA and neutralizing antibody of HPV16, 18 among different age groups. About 16.7% of the women were infected with HPV16, 18, or both.</p><p><b>CONCLUSION</b>In Funing county of Jiangsu province, most women aged 18-45 years has no immunity to HPV16 and 18, indicating that they are appropriate targets for HPV 16/18 vaccination.</p>

Application of CRISPR/Cas9 genome editing technology for inhibition of hepatitis B virus replication / 中华微生物学和免疫学杂志

Objective To evaluate the practicability of using CRISPR/Cas9 genome editing tech-nology for inhibition of hepatitis B virus ( HBV) replication. Methods Two sgRNA targeting sites were de-signed for the S region of HBV genome. The CRISPR/Cas9 expression plasmids specific for HBV were con-structed and then transfected into a cell line expressing HBV genome(HepG2-N10). The cytotoxicity of cells transfected with different expression plasmids were detected by MTT assay. The levels of hepatitis B surface antigen ( HBsAg ) were determined by using chemiluminescent immunoassay ( CLIA ) . The expression of HBV at mRNA level was analyzed by quantitative real-time PCR ( qRT-PCR) . The qPCR was performed for the detection of extracellular and intracellular HBV DNA. The next-generation sequencing ( NGS) Illumina MiSeq Platform was used to analyze HBV genome editing. Results No significant cytotoxic effects were de-tected in HepG2-N10 cells transfected with different expression plasmids. Compared with the cells carrying pCas-Guide-GFP-Scramble, the levels of HBsAg in the supernatants of transfected cell culture harboring pCas-Guide-GFP-G1 and pCas-Guide-GFP-G2 were decreased by 24. 2% (P0. 05), respectively. The levels of HBsAg in cells transfected with pCas-Guide-GFP-G1 and pCas-Guide-GFP-G2 were respectively decreased by 16. 4% (P>0. 05) and 32. 1% (P>0. 05) as compared with that of pCas-Guide-GFP-Scramble transfected group. The expression of HBV at mRNA level was inhibited as indica-ted by the results of qRT-PCR. Moreover, the levels of extracellular HBV DNA were respectively suppressed by 23% (P>0. 05) and 35% (P0. 05) and 18% (P>0. 05). Different types of insertion/deletion mutation were de-tected in HBV genome by high-throughput sequencing. Conclusion HBV-specific CRISPR/Cas9 system could inhibit the expression of HBV gene and the replication of virus. Therefore, the CRISPR/Cas9 genome editing technology might be used as a potential tool for the treatment of persistent HBV infection.